This application is a U.S. national stage of PCT/EP2012/061468 filed on Jun. 15, 2012, which claims priority to and the benefit of Italian Application No. MI2011A001355 filed on Jul. 20, 2011, the contents of which are incorporated herein by reference in their entirety.
The present invention relates to a patch for the transdermal release of diclofenac or a pharmaceutically acceptable salt thereof, in particular diethylamine salt, and thiocolchicoside.
Numerous transdermal formulations in the form of adhesive patches able to release active ingredients of various kinds are known. This administration route is particularly indicated for non-steroidal anti-inflammatory drugs, especially when long-term treatments located in specific areas of the body are required. Transdermal administration reduces the risk of the side effects, especially at gastrointestinal level, which are sometimes encountered with these medicaments.
Diclofenac (2-(2-[2,6-dichlorophenylamino]phenyl)acetic acid) is one of the most widely used non-steroidal anti-inflammatory drugs due to its marked pharmacological activity.
Numerous formulations of diclofenac for topical application are known, in which it is present as sodium salt, potassium salt, diethylamine salt and hydroxyethylpyrrolidine salt in the form of a gel, patch or spray.
Transdermal formulations of diclofenac, in particular of its sodium salt, are disclosed, for example, in EP 524582, EP 582727, U.S. Pat. No. 6,193,996, EP 209975, JP 6056660, WO 99/03461, U.S. Pat. No. 4,999,379, and EP 965626.
Some of the formulations have been developed and are available on the market. Examples of said formations are a 60 g 1% gel with a recommended dose of 2-4 g 3-4 times a day for local treatment of rheumatic or traumatic pain and inflammation of the joints, muscles, tendons and ligaments, and a patch (FLECTOR TISSUGEL or DICLOREUM TISSUGEL) containing 180 mg of diclofenac hydroxyethylpyrrolidine salt to be administered twice a day for the treatment of peri-articular/tendinous inflammatory rheumatological disorders, whether isolated or occurring in the course of systemic disorders, or for the treatment of extra-articular inflammatory rheumatological disorders.
Thiocolchicoside, also known as 3-demethyl-thiocolchicine glucoside, is a glucoside extracted from the seeds of Colchicum autumnale, which possesses a muscle-relaxant, anti-inflammatory, analgesic and anaesthetic action. Examples of available formulations of thiocolchicoside are 30 g 0.25% creams and ointments which contain 250 mg of active ingredient per 100 g of cream, or 75 mg per tube, marketed under the name MUSCORIL. The indicated dose is 2-3 applications a day for the treatment of acute and chronic lumbosciatic pain, cervicobrachial neuralgia, refractory torticollis and post-traumatic and post-operative pain syndromes.
A combination of diclofenac sodium salt and thiocolchicoside in the form of an injectable solution is described in Minerva Anestesiologica, October 1991, pages 1084-1085.
Pharmaceutical compositions in solid form containing a diclofenac salt and thiocolchicoside are disclosed in EP 0 837 684 B 1. Examples of the compositions described are tablets, capsules, topical gels and suppositories, wherein diclofenac is present as sodium salt. The compositions are suitable for immediate or controlled release of the active ingredients they contain.